iDIA-QC: AI-empowered data-independent acquisition mass spectrometry-based quality control.

Quality control (QC) in mass spectrometry (MS)-based proteomics is mainly based on data-dependent acquisition (DDA) analysis of standard samples. Here, we collect 2754 files acquired by data independent acquisition (DIA) and paired 2638 DDA files from mouse liver digests using 21 mass spectrometers across nine laboratories over 31 months. Our data demonstrate that DIA-based LC-MS/MS-related consensus QC metrics exhibit higher sensitivity compared to DDA-based QC metrics in detecting changes in LC-MS status.

Early Identification of Myocardial Microstructural Alterations in Hypertrophic Cardiomyopathy with in Vivo Cardiac Diffusion-Tensor Imaging.

Purpose To explore the diffusion characteristics of hypertrophic cardiomyopathy (HCM) using in vivo cardiac diffusion-tensor imaging (cDTI) and to determine whether cDTI could help identify abnormal myocardium beyond cardiac MRI findings of fibrosis and hypertrophy. Materials and Methods In this prospective study conducted from April to August 2023, participants with HCM and healthy volunteers were enrolled for cardiac MRI evaluation, including cine, late gadolinium enhancement (LGE), T1 mapping, and cDT imaging, using a 3.0-T scanner.

Specifically blocking αvβ8-mediated TGF-β signaling to reverse immunosuppression by modulating macrophage polarization.

Background: Targeting the TGF-β pathway in tumor therapy has proven challenging due to the highly context-dependent functions of TGF-β. Integrin αvβ8, a pivotal activator of TGF-β, has been implicated in TGF-β signaling within tumors, as demonstrated by the significant anti-tumor effects of anti-αvβ8 antibodies. Nevertheless, the expression profile of αvβ8 remains a subject of debate, and the precise mechanisms underlying the anti-tumor effects of anti-αvβ8 antibodies are not yet fully elucidated.

CDC42 deficiency leads to endometrial stromal cell senescence in recurrent implantation failure.

Study Question: Does the downregulation of cell division cycle 42 (CDC42) protein in endometrial stroma lead to endometrial senescence in patients with recurrent implantation failure (RIF), and what is the potential mechanism?

Summary Answer: CDC42 deficiency causes endometrial stromal senescence and decidualization defects, impairing uterine receptivity of RIF patients, via activation of Wnt signaling pathway.

What Is Known Already: Uterine aging is unique due to the cyclic remodeling and decidualization of endometrial tissue. Several transcriptomic studies have reported increased senescence in the endometrium in young patients with RIF.

The epithelial barrier theory and its associated diseases.

The prevalence of many chronic noncommunicable diseases has been steadily rising over the past six decades. During this time, over 350,000 new chemical substances have been introduced to the lives of humans. In recent years, the epithelial barrier theory came to light explaining the growing prevalence and exacerbations of these diseases worldwide.

Prognostic factors for worsening and improvement in multiple sclerosis using a multistate model.

Background: The long-term disease trajectory of people living with multiple sclerosis (MS) can be improved by initiating efficacious treatment early. More quantitative evidence is needed on factors that affect a patient's risk of disability worsening or possibility of improvement to inform timely treatment decisions.

Methods: We developed a multistate model to quantify the influence of demographic, clinical, and imaging factors on disability worsening and disability improvement simultaneously across the disability spectrum as measured by the Expanded Disability Status Scale (EDSS).

Dysregulation of endometrial stromal serotonin homeostasis leading to abnormal phosphatidylcholine metabolism impairs decidualization in patients with recurrent implantation failure.

Study Question: Does abnormal serotonin homeostasis contribute to impaired endometrial decidualization in patients with recurrent implantation failure (RIF)?

Summary Answer: Abnormal serotonin homeostasis in patients with RIF, which is accompanied by decreased monoamine oxidase (MAO) expression, affects the decidualization of endometrial stromal cells and leads to embryo implantation failure.

What Is Known Already: Previous studies have indicated that the expression of MAO, which metabolizes serotonin, is reduced in the endometrium of patients with RIF, and serotonin can induce disruption of implantation in rats. However, whether abnormal serotonin homeostasis leads to impaired decidualization in patients with RIF and, if so, the mechanism involved, remains unclear.

Preclinical study and phase II trial of adapting low-dose radiotherapy to immunotherapy in small cell lung cancer.

Background: Immune checkpoint inhibitors (ICIs) provide modest but unsatisfactory benefits for extensive-stage small cell lung cancer (ES-SCLC). Developing strategies for treating ES-SCLC is critical.

Methods: We preliminarily explored the outcomes of salvage low-dose radiotherapy (LDRT) plus ICI on refractory SCLC patients.

Heart Failure with Normal Natriuretic Peptide Levels and Preserved Ejection Fraction: A Prospective Clinical and Cardiac MRI Study.

Purpose To describe the clinical presentation, comprehensive cardiac MRI characteristics, and prognosis of individuals with predisposed heart failure with preserved ejection fraction (HFpEF). Materials and Methods This prospective cohort study (part of MISSION-HFpEF [Multimodality Imaging in the Screening, Diagnosis, and Risk Stratification of HFpEF]; NCT04603404) was conducted from January 1, 2019, to September 30, 2021, and included individuals with suspected HFpEF who underwent cardiac MRI. Participants who had primary cardiomyopathy and primary valvular heart disease were excluded.

Differential depletion of GluN2A induces heterogeneous schizophrenia-related phenotypes in mice.

Background: Schizophrenia, a debilitating psychiatric disorder, displays considerable interindividual variation in clinical presentations. The ongoing debate revolves around whether this heterogeneity signifies a continuum of severity linked to a singular causative factor or a collection of distinct subtypes with unique origins. Within the realm of schizophrenia, the functional impairment of GluN2A, a subtype of the NMDA receptor, has been associated with an elevated risk.

Neurotoxicity Profiling of Aluminum Salt-Based Nanoparticles as Adjuvants for Therapeutic Cancer Vaccine.

Therapeutic vaccines containing aluminum adjuvants have been widely used in the treatment of tumors due to their powerful immune-enhancing effects. However, the neurotoxicity of aluminum adjuvants with different physicochemical properties has not been completely elucidated. In this study, a library of engineered aluminum oxyhydroxide (EAO) and aluminum hydroxyphosphate (EAHP) nanoparticles was synthesized to determine their neurotoxicity in vitro.

Obesity Is a Major Determinant of Impaired Cardiac Energy Metabolism in Heart Failure with Preserved Ejection Fraction.

Heart failure with preserved ejection fraction (HFpEF) is a major health problem with limited treatment options. Although optimizing cardiac energy metabolism is a potential approach to treating heart failure, it is poorly understood what alterations in cardiac energy metabolism actually occur in HFpEF. To determine this, we used mice in which HFpEF was induced using an obesity and hypertension HFpEF protocol for 10 weeks.

An IgM-like inhalable ACE2 fusion protein broadly neutralizes SARS-CoV-2 variants.

Many of the currently available COVID-19 vaccines and therapeutics are not effective against newly emerged SARS-CoV-2 variants. Here, we developed the metallo-enzyme domain of angiotensin converting enzyme 2 (ACE2)-the cellular receptor of SARS-CoV-2-into an IgM-like inhalable molecule (HH-120). HH-120 binds to the SARS-CoV-2 Spike (S) protein with high avidity and confers potent and broad-spectrum neutralization activity against all known SARS-CoV-2 variants of concern.

The Predictive Value of Cerebral Veins on Hemorrhagic Transformation After Endovascular Treatment in Acute Ischemic Stroke Patients: Enhanced Insights From Venous Collateral Circulation Analysis Using Four-Dimensional CTA.

Rationale And Objectives: A significant complication of endovascular treatment (EVT) is hemorrhagic transformation (HT), which can worsen the outcomes of patients with acute ischemic stroke (AIS). This study aimed to evaluate the predictive value of venous collateral circulation on HT in patients with AIS undergoing EVT.

Materials And Methods: We retrospectively analyzed 126 patients with AIS who received EVT.

HIV post-treatment controllers have distinct immunological and virological features.

HIV post-treatment controllers (PTCs) are rare individuals who maintain low levels of viremia after stopping antiretroviral therapy (ART). Understanding the mechanisms of HIV post-treatment control will inform development of strategies aiming at achieving HIV functional cure. In this study, we evaluated 22 PTCs from 8 AIDS Clinical Trials Group (ACTG) analytical treatment interruption (ATI) studies who maintained viral loads ≤400 copies/mL for ≥24 wk.

β2-microglobulin functions as an endogenous NMDAR antagonist to impair synaptic function.

Down syndrome (DS) is a neurological disorder with multiple immune-related symptoms; however, crosstalk between the CNS and peripheral immune system remains unexplored. Using parabiosis and plasma infusion, we found that blood-borne factors drive synaptic deficits in DS. Proteomic analysis revealed elevation of β2-microglobulin (B2M), a major histocompatibility complex class I (MHC-I) component, in human DS plasma.

Trial of Endovascular Therapy for Acute Ischemic Stroke with Large Infarct.

Background: The role of endovascular therapy for acute stroke with a large infarction has not been extensively studied in differing populations.

Methods: We conducted a multicenter, prospective, open-label, randomized trial in China involving patients with acute large-vessel occlusion in the anterior circulation and an Alberta Stroke Program Early Computed Tomography Score of 3 to 5 (range, 0 to 10, with lower values indicating larger infarction) or an infarct-core volume of 70 to 100 ml. Patients were randomly assigned in a 1:1 ratio within 24 hours from the time they were last known to be well to undergo endovascular therapy and receive medical management or to receive medical management alone.

Genome editing with natural and engineered CjCas9 orthologs.

CjCas9 is one of the smallest CRISPR-associated (Cas9) nucleases for mammalian genome editing. However, it requires a long NRYAC (R = A or G; Y = C or T) protospacer-adjacent motif (PAM), limiting its DNA targeting scope. In this study, we investigated the PAMs of three CjCas9 orthologs, including Hsp1Cas9, Hsp2Cas9, and CcuCas9, by performing a GFP-activation assay.

Trial of Endovascular Treatment of Acute Basilar-Artery Occlusion.

Background: Data from trials investigating the effects and risks of endovascular thrombectomy for the treatment of stroke due to basilar-artery occlusion are limited.

Methods: We conducted a multicenter, prospective, randomized, controlled trial of endovascular thrombectomy for basilar-artery occlusion at 36 centers in China. Patients were assigned, in a 2:1 ratio, within 12 hours after the estimated time of basilar-artery occlusion to receive endovascular thrombectomy or best medical care (control).

Diversity of Species Causing Apple Bitter Rot and Glomerella Leaf Spot in China.

Bitter rot and Glomerella leaf spot (GLS) of apples, caused by species, are major diseases of apples around the world. A total of 98 isolates were obtained from apple fruits with bitter rot, and 53 isolates were obtained from leaves with leaf spot in the primary apple production regions in China. These isolates were characterized morphologically, and five gene regions (, , , -1 and 2) were sequenced for each isolate.

Endovascular Treatment Versus Best Medical Management in Acute Basilar Artery Occlusion Strokes: Results From the ATTENTION Multicenter Registry.

Background: The authors compare the effectiveness and safety of endovascular treatment (EVT) versus best medical management (BMM) in strokes attributable to acute basilar artery occlusion (BAO).

Methods: The present analysis was based on the ongoing, prospective, multicenter ATTENTION (Endovascular Treatment for Acute Basilar Artery Occlusion) trial registry in China. Our analytic sample comprised 2134 patients recruited at 48 sites between 2017 and 2021 and included 462 patients who received BMM and 1672 patients who received EVT.

Impact of nonrandom selection mechanisms on the causal effect estimation for two-sample Mendelian randomization methods.

Nonrandom selection in one-sample Mendelian Randomization (MR) results in biased estimates and inflated type I error rates only when the selection effects are sufficiently large. In two-sample MR, the different selection mechanisms in two samples may more seriously affect the causal effect estimation. Firstly, we propose sufficient conditions for causal effect invariance under different selection mechanisms using two-sample MR methods.

Increased Ingestion of Hydroxy-Methionine by Both Sows and Piglets Improves the Ability of the Progeny to Counteract LPS-Induced Hepatic and Splenic Injury with Potential Regulation of TLR4 and NOD Signaling.

Methionine, as an essential amino acid, play roles in antioxidant defense and the regulation of immune responses. This study was designed to determine the effects and mechanisms of increased consumption of methionine by sows and piglets on the capacity of the progeny to counteract lipopolysaccharide (LPS) challenge-induced injury in the liver and spleen of piglets. Primiparous sows ( = 10/diet) and their progeny were fed a diet that was adequate in sulfur amino acids (CON) or CON + 25% total sulfur amino acids as methionine from gestation day 85 to postnatal day 35.

Clinical Reasoning: A 50-Year-Old Man With Progressive Limb Weakness and Slurred Speech.

A 50-year-old man presented with a 9-month history of progressive left arm weakness and dysarthria. Family history showed that his parents are cousins, and one of his siblings died of motor neuron disease. Brain MRI showed T2-weighted white matter hyperintensities along the course of pyramidal tracts.

Salt-Induced Hepatic Inflammatory Memory Contributes to Cardiovascular Damage Through Epigenetic Modulation of SIRT3.

Background: High salt intake is the leading dietary risk factor for cardiovascular diseases. Although clinical evidence suggests that high salt intake is associated with nonalcoholic fatty liver disease, which is an independent risk factor for cardiovascular diseases, it remains elusive whether salt-induced hepatic damage leads to the development of cardiovascular diseases.

Methods: Mice were fed with normal or high-salt diet for 8 weeks to determine the effect of salt loading on liver histological changes and blood pressure, and salt withdrawal and metformin treatment were also conducted on some high-salt diet-fed mice.